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From Integrated Genomics to Tumor Lineage Dependency

¹ Department of Medical Oncology and ² Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute; ³ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; and ⁴ The Broad Institute of Harvard and MIT, Cambridge, Masachussetts

Requests for reprints: Levi A. Garraway, Department of Medical Oncology, Dana-Farber Cancer Institute, D1542, 44 Binney Street, Boston, MA 02115. Phone: 617-632-6689; Fax: 617-632-3460; E-mail: Levi_Garraway{at}dfci.harvard.edu.

In principle, genomic information derived from tumors should illuminate critical cellular dependencies that are tractable to therapeutic targeting; however, realizing this ideal remains difficult. Using an integrated analysis of high-resolution single nucleotide polymorphism maps and gene expression databases associated with the NCI60 collection cancer cell lines, we identified the transcription factor MITF as an amplified oncogene in melanoma that is critical for anchoring lineage dependence and malignant character. Similar combined genomic approaches may be useful in other cancer types to learn how critical regulators of tumor lineage are linked to genomic alterations in cancer cells. (Cancer Res 2006; 66(5): 2506-8)

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